Neurometabolic profile of mild cognitive impairment using multiplexed edited MRS

使用多重编辑 MRS 分析轻度认知障碍的神经代谢特征

• 批准号: 9759752
• 负责人: Richard Anthony Edward Edden
• 金额: $ 20.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759752
• 关键词: Address; Age; Alzheimer' s Disease; Amyloid beta-Protein; Anaerobic Bacteria; Anterior; Antioxidants; Aspartate; Biological Markers; Brain; Brain imaging; Brain region; Chemicals; Chemistry; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Deposition; Detection; Development; Disease; Energy Metabolism; Functional disorder; Future; Generations; Glutamates; Glutathione; Image; Impaired cognition; Impairment; Individual; Interruption; Lipids; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measurable; Measurement; Measures; Medial; Metabolic dysfunction; Methodology; Methods; Mitochondria; Modeling; N-acetylaspartate; N-acetylaspartylglutamate; Neuraxis; Neurobiology; Neurofibrillary Tangles; Neuromodulator; Neurons; Neurotransmitters; Outcome; Oxidation-Reduction; Oxidative Stress; Pathologic; Patients; Phase; Play; Positron-Emission Tomography; Prevention; Proteins; Reactive Oxygen Species; Resolution; Risk; Role; Sampling Studies; Severities; Signal Transduction; Site; System; Temporal Lobe; Testing; Tissues; amyloid formation; ascorbate; brain tissue; cohort; design; experimental study; gamma-Aminobutyric Acid; healthy aging; in vivo; interest; mild cognitive impairment; mitochondrial dysfunction; neurobiological mechanism; neurochemistry; neuroimaging; neuron loss; neurotransmission; normal aging; oxidative damage; pre-clinical; radiotracer; sex; tau Proteins

Summary Mild Cognitive Impairment (MCI) is a preclinical form of Alzheimer's Disease (AD), characterized by cognitive deficits that are intermediate between those observed in healthy aging and AD. Amnestic multi-domain MCI (aMCI-MD) is a subtype of MCI with high (~40%) rates of conversion to AD, representing a valuable cohort for mechanistic studies of AD pathophysiology at a relatively early phase. The primary pathological/imaging finding in AD/MCI is of abnormal protein deposition in brain tissue, but the mechanisms by which this deposition is initiated and ultimately results in cognitive decline, are poorly understood. Recent developments in edited magnetic resonance spectroscopy (MRS) have substantially accelerated measurements of low- concentration metabolites of key interest in MCI, including redox compounds (glutathione and ascorbate), neurotransmitters and neuromodulators (GABA, glutamate, aspartate and N-acetylaspartylglutamate), and other compounds including the anaerobic product lactate. In this study, we will apply the new editing experiment HERCULES (Hadamard Editing Resolves Chemicals Using Linear Estimation of Spectra) to measure levels of these metabolites in three pathologically important brain regions (medial temporal lobe, anterior and posterior cingulate) in subjects with aMCI-MD and age- and sex-matched healthy controls. We will also test hypothesized relationships between neurochemistry and cognitive outcomes, and between MRS metabolite levels and prior PET imaging of amyloid-β and tau protein deposition.

摘要 轻度认知障碍(MCI)是阿尔茨海默病(AD)的一种临床前形式，以认知为特征 介于健康衰老和阿尔茨海默病之间的缺陷。健忘型多域MCI (aMCI-MD)是MCI的一个亚型，向AD的转化率很高(~40%)，这是一个有价值的队列 阿尔茨海默病病理生理学的机制研究处于相对早期阶段。原发病理/影像 在AD/MCI中发现的是脑组织中异常的蛋白质沉积，但这一机制 沉积是启动的，并最终导致认知衰退，但人们对此知之甚少。最近的发展 在编辑的磁共振波谱(MRS)中，大大加快了对低- MCI中主要感兴趣的浓度代谢物，包括氧化还原化合物(谷胱甘肽和抗坏血酸)， 神经递质和神经调节剂(GABA、谷氨酸、天冬氨酸和N-乙酰天冬氨酸)，以及 其他化合物，包括厌氧产物乳酸。 在本研究中，我们将应用新的编辑实验Hercules(Hadamard Editing Resolves Chemals 使用谱的线性估计)来测量这些代谢物水平在三个病理上重要的 AMCI-MD患者的脑区(内侧颞叶、前扣带回和后扣带回)与年龄和 性别匹配的健康对照组。我们还将测试神经化学和 认知结果以及MRS代谢物水平与先前淀粉样蛋白-β和tau蛋白的正电子发射计算机断层扫描成像之间的关系 证词。